Time trends in the incidence, prevalence, and severity of rheumatoid arthritis: A systematic literature review.

INTRODUCTION: Rheumatoid arthritis (RA) generates a heavy socioeconomic burden. The ability to predict the frequency and severity of socioeconomic effects due to RA is crucial to the development of public health policies. OBJECTIVE: To conduct a systematic literature review of data on the prevalence, incidence, and severity of RA. METHODS: Medline, EMBASE, the Cochrane Library, and online American College of Rheumatology communications were searched for articles on the prevalence and incidence of RA, as well as on selected severity and activity criteria. Relevant articles were then selected by two investigators. RESULTS: Frequency data are conflicting. No proof exists from cohort studies that the incidence of RA has changed over time. Overall, the prevalence of RA is stable or on the rise. Studies consistently demonstrated a decrease in severity over time, with lower activity, fewer extraarticular manifestations, a diminished need for surgery to treat joint destruction, and less severe radiological changes. The excess mortality, in contrast, despite a trend toward a decrease over time, remains significant. CONCLUSION: The activity and deleterious effects of RA have diminished over time, in conjunction with recent therapeutic advances (new drugs and improved patient selection). However, there seems to be no decrease in the frequency of RA, which continues to induce significant excess mortality.

Novel Immunotherapeutic Avenues for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease. It leads to irreversible joint damage, physical handicap, and reduced life expectancy. The past two decades have seen considerable therapeutic advances with the development of biologic treatments to block proinflammatory cytokines or modulate lymphocyte function, followed by the development of small molecules to target intracellular signaling. Nevertheless, only a minority of patients can achieve disease remission, especially long term, warranting further investigation into newer therapeutic options. Targeting single proinflammatory pathways may not be sufficient, as suggested by variable results with T helper (Th)-17-related cytokine blockade. Multilevel information from 'omics' techniques along with data from mechanistic studies might facilitate the identification of pivotal checkpoints in RA disease pathogenesis and the subsequent development of new effective treatments.

Cachexia and adiposity in rheumatoid arthritis. Relevance for disease management and clinical outcomes.

Altered body composition is a frequent finding in rheumatoid arthritis and is associated with the two major outcomes of the disease: disability and cardiovascular mortality. It is estimated that up to two thirds of patients may be affected by loss of lean mass, the so-called rheumatoid cachexia. Hence, body weight being equal, the relative amount of lean mass is lower and that of body fat is higher in rheumatoid arthritis patients vs. healthy controls. Both disease-related factors and other factors, like drug treatments, physical activity and nutrition contribute to modify body composition in rheumatoid arthritis. The effect of pharmacological treatments, and notably of anti-TNF drugs, on body composition is controversial. Conversely, training programs to stimulate muscle growth can restore lean mass and reduce adiposity. There is good evidence that amelioration of body composition ameliorates function and reduces disability. Currently, there is no evidence that interventions that modify body composition can reduce cardiovascular morbidity and mortality in rheumatoid arthritis.

Targeting IL-6 for the treatment of rheumatoid arthritis: Phase II investigational drugs.

INTRODUCTION: IL-6 is a key cytokine in the pathogenesis of rheumatoid arthritis (RA). The clinical efficacy of tocilizumab (TCZ), a humanized anti-IL6-receptor mAb, confirmed the value of IL-6 blockade in this disease. A number of new anti-IL-6 biologics are currently in Phase I - III of clinical development for RA. AREAS COVERED: This article reviews the available results from Phase II trials of investigational anti-IL-6 agents in RA. The authors discuss the potential relevance of alternative IL-6-blocking agents, with regard to their specific molecular targets in IL-6 signaling pathways and to the main open questions in the clinical research agenda for anti-IL-6 biologics. EXPERT OPINION: The results of Phase II trials of new anti-IL-6 biologics show promising results in terms of efficacy. The most frequently reported adverse events were not unexpected based on previous experience with TCZ. Further evidence is needed to appraise whether the difference in molecular structure or in the specific target of new anti-IL-6 biologics might result in added therapeutic value over TCZ. New data from Phase III trials that provides a head-to-head comparison against TCZ and anti-TNF agents with or without methotrexate background treatment are expected in the future.

Infectious sacroiliitis: a retrospective, multicentre study of 39 adults.

BACKGROUND: Non-brucellar and non-tuberculous infectious sacroiliitis (ISI) is a rare disease, with misleading clinical signs that delay diagnosis. Most observations are based on isolated case reports or small case series. Our aim was to describe the clinical, bacteriological, and radiological characteristics of ISI, as well as the evolution of these arthritis cases under treatment. METHODS: This retrospective study included all ISI cases diagnosed between 1995 and 2011 in eight French rheumatology departments. ISI was diagnosed if sacroiliitis was confirmed bacteriologically or, in the absence of pathogenic agents, if clinical, biological, and radiological data was compatible with this diagnosis and evolution was favourable under antibiotic therapy. RESULTS: Overall, 39 cases of ISI were identified in adults, comprising 23 women and 16 men, with a mean age at diagnosis of 39.7 ± 18.1 years. The left sacroiliac joint (SI) was affected in 59% of cases, with five cases occurring during the post-partum period. Lumbogluteal pain was the most common symptom (36/39). Manipulations of the SI joint were performed in seven patients and were always painful. Mean score for pain using the visual analogue score was 7.3/10 at admission, while 16 patients were febrile at diagnosis. No risk factor was found for 30.7% of patients. A diagnosis of ISI was only suspected in five cases at admission. The mean time to diagnosis was long, being 43.3 ± 69.1 days on average. Mean C-reactive protein was 149.7 ± 115.3 mg/l, and leukocytosis (leukocytes ≥ 10 G/l) was uncommon (n = 15) (mean level of leukocytes 10.4 ± 3.5 G/l). Radiographs (n = 33) were abnormal in 20 cases, revealing lesions of SI, while an abdominopelvic computed tomography (CT) scan (n = 27) was abnormal in 21 cases, suggesting arthritis of the SI joints in 13 cases (48.1%) and a psoas abscess in eight. Bone scans (n = 14) showed hyperfixation of the SI in 13 cases. Magnetic resonance imaging (MRI) (n = 27), when focused on the SI (n = 25), directed towards the diagnosis to ISI in 25 cases. Pathogenic agents were isolated in 33 cases (84.6%) by means of articular puncture (n = 16), blood culture (n = 14), cytobacteriological examination of urine (n = 2), or puncture of the psoas (n = 1).Gram-positive cocci were the mostly isolated common bacteria, with a predominance of staphylococci (n = 21). The most frequently isolated gram-negative bacillus was Pseudomonas aeruginosa (n = 3). Evolution was favourable in 37 out of 39 patients under prolonged antibiotic therapy (mean duration 3.01 ± 1.21 months). CONCLUSION: Our series confirmed that the clinical manifestations of ISI usually lead to delayed diagnosis. Based on our results, we suggest performing an MRI of the spine and SI in clinical situations characterised by lumbogluteal pain and symptoms of an infectious disease, such as fever.